Flu Shot Benefits for Elderly Questioned

Action Points

Explain to interested patients that the flu vaccine has been shown to reduce morbidity and mortality from flu, but some studies have suggested it also has an effect on all-cause mortality among the elderly.

Note that this analysis suggests that observations of such a benefit among the elderly were confounded by a so-called "healthy-user effect," in which those least likely to die are also most likely to get vaccinated.

The finding, from a case-control study of 704 people admitted to the hospital with community-acquired pneumonia outside of the flu season, calls into question previous observational studies that found a substantial benefit, according to Dean Eurich, Ph.D., and colleagues at the University of Alberta.

Instead, what those studies observed was probably a "healthy-user effect" that confounded the results, Dr. Eurich and colleagues argued in the

Sept. 1 issue of the American Journal of Respiratory and Critical Care Medicine.

The researchers called for "much needed" randomized trials of flu vaccines in the elderly to clarify the issue.

Because influenza is seasonal, the off-season provides a control period, in which flu vaccine would not be expected to show a benefit. If there were a benefit, the researchers argued, it must be the product of a bias of some sort.

To test the question, they looked at 1,813 adults with community-acquired pneumonia admitted to six hospitals outside of influenza season in Edmonton's Capital Health region.

The study cohort consisted of 352 people (most of them over 65) who had been vaccinated against the flu and 352 matched controls. Data were collected prospectively and included age, sex, comorbidities, and prescription medications.

But the data also included clinical characteristics (such as documentation of advanced directives and smoking status), immunization history, premorbid functional status, socioeconomic status, and the Pneumonia Severity Index.

Overall, 81 patients (or 12%) died in the hospital and, in unadjusted analyses, vaccinated patients were significantly less likely to die than were controls -- 28 versus 53. The odds ratio was 0.49 with a 95% confidence interval from 0.30 to 0.79, which was significant at P=0.004.

The odds ratio was not substantially changed after adjustment for what the researchers called "the typical adjustments possible in large administrative databases" -- age, gender, nursing home residence, comorbidities, and number of medications.

"While such a reduction in all-cause mortality would have been impressive, these mortality benefits are likely implausible," Dr. Eurich said in a statement, if only because none of the patients had the flu.

And indeed, when the researchers adjusted for all available data, the analysis yielded a smaller -- and no longer significant -- odds ratio for death of 0.81, with a 95% confidence interval from 0.35 to 1.85.

The researchers argued that "the mortality benefits of influenza vaccination may have been largely overestimated," since accounting for disease severity and measures of functional status caused "a striking and highly significant association (to become) attenuated and non-significant."

The most likely reason for the apparent benefit is the healthy-user effect, according to senior author Sumit Majumdar, M.D.

The term is used by clinicians to describe patients who are well-informed about their health, exercise regularly, do not smoke or have quit, drink in moderation, watch what they eat, take medications as prescribed, and get vaccinated each year.

"Such attributes are almost impossible to capture in large scale studies using administrative databases," Dr. Majumdar said in a statement.

Indeed, the finding "directly demonstrates" the presence of such a bias, according to Lisa A. Jackson, M.D., of the Group Health Center for Health Studies in Seattle.

Writing in an accompanying editorial, Dr. Jackson said she and her colleagues have observed a similar apparent reduction in mortality among vaccinated patients even in the non-flu season.

A key message of the study is the need for enough information to reduce, if not eliminate, bias, Dr. Jackson said.

But, she added, "the signs point to a hard road ahead in the quest for less biased estimates of influenza vaccine effectiveness in older adults."

Among other things, she said, it will be difficult to conduct randomized placebo-controlled trials in the U.S. or other places where guidelines call for the routine vaccination of the elderly.

The study was supported by the Alberta Heritage Foundation for Medical Research, Capital Health, Abbott Canada, Pfizer Canada, Jannsen-Ortho Canada, and the Canadian Institutes of Health Research.

The researchers said they had no conflicts. Dr. Jackson reported financial links with Novartis, Sanofi Pasteur, GlaxoSmithKline, and Wyeth for participation in multi-center trials of various vaccines.

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